摘要
细胞色素P450酶能够在正常的生理环境下活化烃类上的氢,这在化学上具有重要的意义。P450酶的催化作用是通过活性中心的血红素催化作用产生的。由于活性中心中铁的特殊结构及其与卟啉环和蛋白质的配位作用,使得血红素对于烃类的催化具有在高自旋和低自旋态上具有双态反应的特性。量子力学中的密度泛函理论能够为我们提供有利工具来探究这个反应。本文通过DFT理论探究了P450酶的血红素在不同自旋态上对于花生四烯酸的羟基化和环氧化的催化反应。通过分析反应过程中的电荷、电子自旋以及结构的变化,原子水平上揭示了血红素对于花生四烯酸的代谢过程,特别是反应过程中过渡态结构和决速步骤。血红素酶对于烃类催化机理的研究有助于我们设计合理的药物。
Cytochrome P450 is an important enzyme to activity to hydrogen of hydrocarbon in vivo. In this paper, we applied density functional theory(DFT) to explore hydroxylation and epoxidation reaction of arachidonic acid by cytochrome P450. A detailed analysis of the charge and energy show the interaction between the arachidonic and heme moieties. This study help us to understand heme in P450 catalyzed the arachidonic acid from atom level, especially on the transition structure and rate determining step. The theoretical study helps us to design a rational drug.
引文
[1]Laethem,R.M.;Balazy,M.;Falck,J.R.;Laethem,C.L.;Koop,D.R.,The Journal of biological chemistry 1993,268(17):12912
[2]Shaik,S.;Kumar,D.;de Visser,S.P.;Altun,A.;Thiel,W.Chemical reviews 2005,105(6):2279.